1. Technical Field
This document relates to methods and materials involved in assessing renal structural alterations (e.g., renal fibrosis) as well as methods and materials involved in assessing outcomes. For example, this document relates to methods and materials for using the level of urinary C-type natriuretic peptide (CNP) (e.g., a urinary to plasma CNP ratio) or the level of plasma CNP to determine whether or not a mammal is developing renal structural alterations (e.g., renal fibrosis, glomerular basement thickening, swollen podocytes, and foot processes effacement). This document also relates to methods and materials for using the level of urinary or plasma CNP, which can include six molecular CNP forms, levels to identify heart failure patients having an increased likelihood of experiencing a poor outcome and who may have disease processes known to involve the kidney including, but not limited to, heart failure, hypertension, diabetes, metabolic syndrome, and chronic kidney disease
2. Background Information
C-type natriuretic peptide (CNP) is part of the natriuretic peptide family, produced in the kidney as well as the endothelium and can be detected in the plasma and urine. It is synthesized as the precursor 103 amino acid (AA) protein, proCNP (AA 1-103), which is then cleaved into CNP-53 (AA 51-103) and NT-proCNP (AA 1-50) by the intracellular endoprotease furin. Additional downstream processing, by an unknown enzyme, cleaves CNP-53 to give rise to the primary biologically active form CNP-22 (AA 82-103) and its amino-terminal, NT-CNP-53 (51-81).
CNP possesses potent anti-fibrotic and anti-proliferative properties through the activation of the natriuretic peptide receptor B (NPR-B), otherwise known as guanylyl cyclase receptor B (GC-B), and the generation of the second messenger 3′,5′-cyclic guanosine monophosphate (cGMP). CNP has limited natriuretic and diuretic actions.